Type .gamma. interferon (hereinafter sometimes abbreviated as IFN-.gamma.) is produced by immunocompetent cells under circumstances such that blastoid transformation of lymphocytes or production of lymphokines takes place and accordingly it is also called immune interferon. IFN-.gamma. is said to have higher antiproliferative or antitumor activity as compared with IFN-.alpha. and IFN-.beta., and therefore it is much expected of from the clinical application viewpoint. However, due to various limitations, such as requirement of fresh lymphocytes for its production, any efficient production systems have not been established yet.
Recently, the recombinant DNA technology has come into wide use and, as a result, a complementary DNA (cDNA) for IFN-.gamma. has been cloned and its nucleotide sequence and the amino acid sequence expected therefrom have been disclosed. It is now possible to express the cDNA or other chemically synthesized genes in a variety of hosts [Gray, P. W. et al., Nature, 295, 503 (1982); Devos, R. et al., Nucleic Acids Res., 10, 2487 (1982); Tanaka, S. et al., Nucleic Acids Res., 11, 1707 (1983); etc.].
Furthermore, the method of purification using monoclonal antibodies has enabled large-scale production of IFN-.gamma. by the recombinant DNA technology (recombinant IFN-.gamma.; hereinafter sometimes referred to as rIFN-.gamma.) [cf. EPC (laid open) No. 0103898], and its clinical use is expected to be near at hand.
However, rIFN-.gamma. thus obtained is unstable, tending to form a dimer or polyner. Therefore, it is difficult to purify it or make it into pharmaceutical preparations. Highly sophisticated techniques are required for its purification and the preparation of dosage forms containing it.
The present inventors considered that the above drawback of the known rIFN-.gamma. might be due to the two Cys residues occurring in the N-terminal portion thereof and, based on this idea, have now succeeded in producing novel polypeptides which are at least equivalent in biological activity to rIFN-.gamma. and resistant to dimerization or polymerization and have thus completed the present invention.